tbuckley/cabot-search huggingface dataset:
Abstract 12809: Cirrhotic Cardiomyopathy Before Orthotropic Liver Transplantation is Associated With Major Adverse Cardiac Events at 13-Months Post Orthotropic Liver Transplantation
Authors: Saad A Ali, Huseyin E Arman, Hani Shamseddeen, Nathaniel Elsner, Sean C Johnson, Hussein I Elsemesmani, Kavish Patidar, Eric Orman, Joseph Zenisek, Kyle A Frick
Journal: Circulation (2022)

Background: Major adverse cardiac events (MACE) are a leading cause of morbidity and mortality after orthotopic liver transplantation (OLT). Cirrhotic cardiomyopathy (CCM) is relatively common and a source of MACE in patients after OLT. Initial diagnostic criteria based on transthoracic echocardiogram (TTE) were described in 2005 and revised in 2019 with echocardiographic advancements (Table 1). We sought to identify CCM related predictors of MACE at 13 months post-OLT. Methods: This is a retrospective study of adult patients who underwent OLT between 2009-2019. All patients had TTE’s within one year pre-OLT and one month to 13 months post-OLT. We excluded TTE’s within one-month post-OLT to reduce contributions from stress cardiomyopathy. Patients with a left ventricular ejection fraction less than 50% pre-OLT were excluded. MACE was defined as death, MI, CHF hospitalization, or cardiac arrest. Multivariable Cox regression was used to identify independent predictors of MACE. Results: Of 568 OLT patients screened, 131 met inclusion criteria for this study. There were 103 and 23 patients who met 2005 and 2019 criteria, respectively. During the 13 month follow up period, 42 patients had MACE. Compared to those without MACE, patients with MACE had more ascites (93 vs 70%, p 0.003), hepatorenal syndrome (HRS) (17 vs 4%, p 0.019), delayed OLT &gt;10 days after admission (19 vs 7%, p 0.033), pre-OLT CCM per 2005 criteria (90% vs 73%, p 0.023), and lower diastolic blood pressure (60.81 vs 66.88, p 0.014). There was no difference in pre-OLT CCM per 2019 criteria (19 vs 17%, p 0.758) or MELD-Na score (21.24 vs 19.40, p 0.166). In multi-variable cox regression analysis adjusted for diastolic blood pressure, HRS, ascites, and OLT timing during admission, CCM per 2005 criteria remained significant as seen in Figure 1 (Hazard Ratio = 3, p 0.038). Conclusion: CCM per 2005 criteria is an independent predictor of MACE at 13 months post-OLT while CCM per 2019 criteria is not.
Abstract 14421: Avoid Pericardiectomy in Transient Constrictive Pericarditis
Authors: Zachary S Yaker, Muhammad Majid, Richard Linchangco, Alveena Syed, Allan L Klein
Journal: Circulation (2022)

Case Presentation: A male in his 40s presented for chest pain, dyspnea and bilateral leg edema. He has a history of hypertrophic cardiomyopathy treated with septal myectomy complicated by constrictive pericarditis (CP) that was treated with right-sided pericardiectomy, NSAIDs, colchicine, and steroids. Echo showed LVEF of 55% with thickening of the pericardium, abnormal septal bounce, tethering of the right atrium, respiratory variation in flow across the mitral and tricuspid valves and IVC plethora. Cardiac MRI showed diffuse mild thickening of residual left-sided pericardium, mild diffuse circumferential pericardial enhancement, mild diastolic septal bounce, diastolic restraint, exaggerated inspiratory flattening and conical deformity of the ventricles without evidence of myocardial inflammation or scarring. Right heart catheterization showed near equalization of RV and LV pressures, RV and LV respiratory concordance, aortic pulsus paradoxus with an inspiratory decrease of 15 mmHg, and Kussmaul’s sign with an inspiratory increase in RA pressure of 68 mmHg. Left heart catheterization showed normal coronaries. The patient was diagnosed with CP and underwent repeat pericardiectomy and was treated with NSAIDs and diuretics. On follow-up, patient had symptomatic improvement but still had evidence of residual constriction on echocardiogram. Discussion: Pericardiectomy is the definitive treatment for CP, however it carries high morbidity and mortality rates. Recurrence of constrictive pericarditis requiring repeat pericardiectomy is very rare and risk factors for recurrence are not well-defined. His initial pericardiectomy was complicated with evidence of active visceral epicarditis with epicardial constriction. This case suggests that active inflammation at the time of pericardiectomy is a potential risk factor for recurrent CP requiring repeat pericardiectomy, and surgery should be deferred until the active inflammation has subsided.
Abstract 12823: Racial Disparities and Geographic Variation in Anticoagulant Treatment Among Medicare Beneficiaries With Non-Valvular Atrial Fibrillation in the United States
Authors: Amiee Kang, Virginia Noxon, Nipun Atreja, Dionne Hines, Jenny Jiang, Mauricio Ferri
Journal: Circulation (2022)

Introduction: Little is known about racial disparities and the geographic variation in oral anticoagulant (OAC) use throughout the United States (US) since the approval of direct oral anticoagulants (DOACs) as a safe alternative treatment compared to warfarin for non-valvular atrial fibrillation (NVAF). Methods: Patients with NVAF were selected from the US Centers for Medicare &amp; Medicaid Services claims database (01JAN2013 to 31DEC2016). The final population consisted of patients with 12 months of health plan enrollment before and after the NVAF diagnosis and with a baseline CHAD 2 S 2 -VASc ≥ 2. Each patient was assigned a 3-digit zip code based on their primary residence. Results were stratified by race. Geographic variations within each race and differences between races were visualized using ArcGIS Pro software. Results: Of the 2,756,097 patients with NVAF and CHAD 2 S 2 -VASc ≥ 2, majority (88.9%) were White, and 6.3% were Black. Age and HASBLED scores ranged from 79 (Black) to 81 (White) and 3.4 (White) to 3.9 (Black), respectively. The CHAD 2 S 2 -VASc and CCI scores ranged from 5.1 (White) to 5.5 (Black) and 3.0 (White) to 4.3 (Black), respectively. In general, Black patients had a higher untreated rate with an OAC than Whites (Figures 1 and 2). There were also geographic variations in treatment rates mostly noted among Whites with lower rates in the mid-west compared to the south and west (Figure 2). Conclusion: OAC use by race varies considerably by 3-digit zip code in the US. Higher untreated rates and use of warfarin over DOACs in the Black population indicate a potential target for further research into disparities between races in availability of anticoagulant treatment.
Abstract 14247: Speckle Tracking Echocardiography for Assessment of Left Ventricular Remodeling in Soccer Athletes
Authors: Cássia Aparecida Silva, HAROLDO C ALEIXO, Bruno R Nascimento, André Gualberto J Alves, LUZ MARINA TACURI CHAVEZ, Kaciane Oliveira, Taylla Mendes Silva, Luana D Pereira, Bruno Galdino, Lucas Fraga, Thales Aleixo, Luiza P Santos, Lucas C Diamante, Arthur M Amaral, João Pedro B Rocha, Lucas Ruback, Leonardo Ribeiro, Leandro L Durães, Antonio L Ribeiro, Craig A Sable, Andrea Z Beaton, Maria D Nunes, Marcia Barbosa
Journal: Circulation (2022)

Introduction: Speckle-tracking echocardiography (STE)-derived strain is a sensitive tool to detect early signs of exercise-induced cardiac remodeling in athletes, which may contribute to differentiate between physiological and pathological adaptation to sports. Objective: We aimed to assess the effect of regular athletic training on myocardial function assessed by STE in soccer players. Methods: We prospectively enrolled teenager soccer players who participate in regular training in a professional soccer team from Minas Gerais, Brazil. All asymptomatic athletes without known cardiovascular disease and with a structurally normal heart on transthoracic echocardiogram were included. Global longitudinal strain (GLS) by STE was performed in each athlete and measured offline using EchoPAC (GE) software. GLS was categorized according to absolute value |x| and GLS &lt;16% was considered decreased, 16% to 18% borderline and &gt;18% normal. Clinical, demographic and echocardiographic variables associated with reduced and borderline GLS were assessed by logistic regression. Results: The study population consisted of 352 male trained athletes with a mean age of 14 years (range 9 to 20), body mass index (BMI) of 20.4 ± 2.8 kg/m2, and left ventricular ejection fraction (LVEF) of 70 ± 6%. In the overall study population, the mean GLS value was -19.6 ± 2.2%, decreased in 13 athletes (3.7%) and borderline in 57 athletes (16.3%). In multivariable logistic regression analysis, BMI (odds ratio [OR] 1.38; 95% confidence interval [CI] 1.21 - 1.59; p&lt;0.001), LVEF (OR 0.94; 95% CI 0.91 - 0.98; p=0.004), left atrial volume (OR 0.89; 95% CI 0.83 - 0.95; p=0.001), E/e' ratio (OR 1.52; 95% CI 1.07 - 2.11; p=0.019) and E/A ratio (OR 0.37; 95% CI 0.18 - 0.78; p=0.009) were independently associated with reduced and borderline GLS. The model was well calibrated and with good discrimination, yielding a C-statistic of 0.78 (95% CI 0.72 - 0.85). Conclusions: This study provides sport-specific GLS values in the setting of normal LVEF in young athletes. Determinants of abnormal GLS include diastolic and systolic echocardiographic parameters related to exercise adaptation. Decreased myocardial deformation by STE may reflect a forthright relaxed cardiac state rather than underlying pathology.
Abstract 14192: Effect of Aspirin Dosing in Patients Treated With P2Y12 Inhibitors for Secondary Prevention of Cardiovascular Events
Authors: Saket Girotra, Amanda Stebbins, Lisa M Wruck, Danielle Riley, Sunil Kripalani, Daniel Munoz, Mark B Effron, Kamal gupta, Jeffrey Whittle, Catherine Benziger, Li Zhou, Peter M Farrehi, Tamar S Polonsky, Faraz S Ahmad, Matthew T Roe, Russell Rothman, Robert A Harrington, Adrian F Hernandez, William S Jones
Journal: Circulation (2022)

Background: The ADAPTABLE was a pragmatic randomized controlled trial that found no difference between high dose vs low dose aspirin for secondary prevention of ischemic or bleeding events. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. Methods: Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). Ticagrelor was not permitted due to a black box warning with high dose aspirin. The primary effectiveness endpoint was a composite of myocardial infarction, stroke, or death and the primary safety endpoint was hospitalization for major bleeding. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Results: Of the 13,815 (91.6%) participants with available data, 3,051 (22.1%) were on a P2Y12 inhibitor at baseline (clopidogrel: 93.4%; prasugrel: 6.6%). P2Y12 inhibitor use was associated with higher risk of the primary effectiveness endpoint (10.86% vs. 6.31%; adjusted HR 1.44 95% CI 1.22-1.62) but was not associated with bleeding (0.53% vs. 0.95%; adjusted HR:1.42; 95% CI 0.91, 2.22). We found no interaction in the relative effectiveness and safety of high vs. low dose aspirin by P2Y12 inhibitor use (Table, P interaction 0.09 and 0.73 for primary effectiveness and safety endpoint, respectively). Aspirin dose switching and discontinuation occurred in 28.6% of patients. Although this was more common in high dose vs. low dose aspirin, the above rates did not differ between the P2Y12 and non-P2Y12 groups. Conclusion: In this pre-specified subgroup analysis of a large, pragmatic trial, we found that the relative effectiveness and safety of high dose vs. low dose aspirin was not modified by baseline use of P2Y12 inhibitors. Decisions regarding aspirin dosing should be individualized based on clinical factors and patient preference, regardless of P2Y12 inhibitor use.
Abstract 13760: Long-Term Cancer Risk After Acute Coronary Syndrome in Selected Urban and Rural Areas. The ABC-7b* Study on Heart Disease
Authors: Heba T Mahmoud, Rosa Palmieri, Rocco Cordiano, Fiorella Cavuto, Mattia Pasquinucci, moemen mohammed mahmoud, Francesco Bagato, Giuseppe S Berton
Journal: Circulation (2022)

Background Increased cancer risk has been reported in patients with acute coronary syndrome (ACS). We attempted to investigate the geographic differences in this risk. Methods: In this prospective study, we enrolled 525 ACS patients admitted to 3 hospitals in Veneto region of Italy and discharged alive and free from neoplasia. Patients’ residency was classified into 2 urban and 2 nearby rural areas. We report the risk of neoplasia associated with smoking as a comparison. Results: With 3 exceptions, all patients completed a 24-year follow-up unless pre-empted by death. Urban (46%) and rural (54%) residents shared most of their baseline demographic and clinical characteristics. During the follow-up period, which represented 5851 person-years, 114 (22%) patients developed cancer. The cancer incidence rate was 17 and 22 per1000 person-years for urban and rural areas, respectively. No difference in cancer onset risk was found between urban and rural areas or between southern and northern provinces (HR 1.3; 95%CI 0.9–1.9; p = 0.21 and HR 1.4; 95% CI 0.9–2.0; p = 0.08, respectively) according to the unadjusted Cox regression analysis. Geographic areas, however, showed a strong positive interaction, with risk increasing from the urban to rural areas from southern to northern provinces (HR 2.9; 95% CI 1.3–6.5; p = 0.01). The fully adjusted model provided similar results. The HR for malignancy onset after ACS by smoking habit was (1.3; 95% CI 0.8–2.0; p = 0.26) in the unadjusted Cox regression model. Conclusion The present prospective study shows that the cancer onset risk among unselected ACS patients in Italy’s Veneto region significantly differs by geography with the northern rural area having the highest risk. The risk seems to be higher than that observed with smoking habits. Figure 1. Graphical representation of the interaction analysis.
Abstract 13413: Clinical Outcomes of Right Ventricular Systolic Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis
Authors: Natnicha Leelaviwat, Poemlarp Mekraksakit, Jakrin Kewcharoen, Sittinun Thangjui, Sakditad Saowapa, Angkawipa Trongtorsak
Journal: Circulation (2022)

Background: Right ventricular systolic dysfunction (RVSD) is a known predictor of survival in patients with heart failure with reduced ejection fraction. However, the association between RVSD and heart failure with preserved ejection fraction (HFpEF) remains unclear. Objectives: We, therefore, conducted a systematic review and meta-analysis to assess the association between RVSD and HFpEF. Method: Two investigators independently searched the databases of MEDLINE and EMBASE from inception to April 28, 2022 to identify the study that reported outcomes of interest in HFpEF with or without RVSD. Primary outcome was a composite outcome of death and heart failure rehospitalization. Secondary outcome was all-cause mortality. RVSD was defined as right ventricular ejection fraction &lt; 50% by echocardiography or cardiovascular magnetic resonance. Data from each study were combined using the random-effects model to calculate pooled hazard ratio (HR) and 95% confidence interval (CI). Results: Five observational studies involving 1,181 patients with HFpEF from December 2014 to May 2021 were included in our meta-analysis. The presence of RV systolic dysfunction in HFpEF patients was associated with a significantly higher risk of composite outcome of death and heart failure rehospitalization (HR 3.29; 95% CI 1.92-5.65; I2 = 52%) and all-cause mortality (HR 1.72; 95% CI 1.16-2.53; I2 = 68%) compared to those without RV systolic dysfunction. Conclusions: Our meta-analysis demonstrates that HFpEF patients with RVSD is associated with a worse outcome compared to those without RVSD.
Abstract 14820: Pericardial Adipose Tissue Thrombospondin-1 Associates With Anti-Angiogenesis in Ischemic Heart Disease
Authors: Bulbul Ahmed, Melissa G Farb, Emily Sroczynski, Shakun Karki, Niloo Edwards, Noyan Gokce
Journal: Circulation (2022)

Defective angiogenesis contributes to mechanisms of ischemic heart disease. Accumulation of ectopic pericardial adipose tissue has been associated with cardiovascular complications which, in part, may relate to adipose tissue-derived factors. We sought to characterize adipose tissue microvascular angiogenic capacity in individuals undergoing elective cardiac surgeries including aortic, valvular, and coronary artery bypass grafting (CABG). Pericardial fat was collected intraoperatively and examined for capillary sprouting capacity using an established ex vivo Matrigel-based methodology quantified for growth over seven days. Angiogenic capacity was significantly blunted (2.5-fold, p&lt;0.001) in subjects with CAD (age 59±2 years, BMI 32±1 kg/m 2 , LDL-C 92±45 mg/dl, n=37) compared to age-, BMI-, and LDL-cholesterol matched individuals without angiographic obstructive CAD (age 56±4 years, BMI 32±1 kg/m 2 , LDL-C 110±40 mg/dl, n=14). To garner potential mechanistic insight, we performed transcriptomic analyses using quantitative RT- PCR for select angiogenic regulators. We observed no significant differences in pericardial fat gene expression for pro-angiogenic mediators vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor-2 (FGF-2), and angiopoietin-1, or anti-angiogenic factors including soluble fms-like tyrosine kinase-1 (sFlt-1) and endostatin. In contrast, mRNA expression of anti-angiogenic thrombospondin-1 (TSP1) was significantly upregulated (2-fold, p&lt;0.05) in CAD subjects compared to the non-CAD group, which was confirmed by protein western-immunoblot analysis. Plasma concentrations of TSP-1 quantified by ELISA were not significantly different between the two groups. In summary, pericardial fat in subjects with CAD may be associated with an anti-angiogenic transcriptome linked to functional defects in vascularization capacity. Local paracrine actions of TSP1 in adipose depots surrounding the heart may play a role in mechanisms of ischemic heart disease.
Abstract 12847: Atrial Fibrillation and Atrial Flutter: What Are the Substrate Differences Seen in 3D Panoramic Optical Mapping?
Authors: Lea Melki, Najla Saadallah, Ruiping Ji, Elaine Y Wan
Journal: Circulation (2022)

Background: Panoramic optical mapping (POM) is an effective tool for 3D visualization and analysis of action potential duration (APD) heterogeneity, a key driver for initiation and persistence of reentry. POM may elucidate cardiac electrophysiological predisposition to develop chaotic arrhythmia such as atrial fibrillation (AF) or organized arrhythmia such as atrial flutter (AFL). Objective: To determine the APD differences in AF and AFL in a transgenic (TG) murine model. Methods: We performed high resolution POM with 4 simultaneous CMOS cameras on 14 Langendorff perfused TG murine hearts (SCN5A mutation at lidocaine binding site F1759A) with spontaneous AF and AFL. We generated serial 2D activation and APD maps in normal sinus rhythm (NSR), while phase movies were created in AF/AFL. All optical maps were then reconstructed in 3D. We averaged the APD80 and APD dispersion values over each atrial chamber and compared the mean differences: i) within AF and AFL across right atrium (RA) and left atrium (LA); and ii) within RA and LA across AF and AFL. Results: AF (n=7) and AFL (n=7) were present at baseline (8/14) or induced by 10Hz burst pacing (6/14). Mean APD80 in RA/LA was: 57.03 ± 4.66 / 50.93± 3.38ms (p&lt;0.05) in AF vs 77.18 ± 4.30 / 58.25 ± 3.88ms (p&lt; 0.01) in AFL, and mean dispersion: 6.23 ± 1.04/ 7.25± 1.71ms in AF vs 5.49 ± 0.80/ 8.42 ± 1.15ms (p&lt;0.01) in AFL. High mean APD80 in the RA with low intra-atrial dispersion in the RA lead to AFL rotational reentry cores, while lower overall APD80 values with high intra-atrial dispersion in the LA resulted in the presence of AF phase singularity points. Conclusion: Development of AF was associated with high intra-atrial APD dispersion in NSR, whereas AFL was associated with high inter-atrial APD dispersion in NSR (1.4-fold higher mean APD80 in the RA). Certain atrial APD dispersion patterns observed in NSR are associated with development of chaotic vs. organized atrial arrhythmias.
Abstract 13625: Autophagy Plays a Key Role in the Loss of Nitric Oxide Signaling and Endothelial Dysfunction in Pulmonary Vascular Diseases
Authors: Ying Liang, Wojciech Ornatowski, Qing Lu, Xutong Sun, Alejandro E Garcia, Evgeny A Zemskov, Emin Maltepe, Jeffrey R Fineman, Kim Tieu, Ting Wang, Stephen M Black
Journal: Circulation (2022)

Introduction: Congenital heart defects (CHDs) are the most common type of birth defect. Children or infants with CHD often develop pulmonary vascular diseases (PVD) due to increased pulmonary blood flow and pressure. Unfortunately, there is no effective therapy to limit the shared pathophysiologic features of pulmonary endothelial dysfunction and vascular remodeling. Autophagy, a lysosome-dependent proteolytic pathway, enables cells to sequester portions of cytosolic proteins or damaged organelles into autophagosomes and degrade them in autolysosomes. Studies have found that autophagy participates in pulmonary hypertension, acute lung injury, lung cancer, and other pulmonary diseases. Hypothesis: Autophagy plays a key role in the development of pulmonary endothelial dysfunction in PVD associated with CHD. Methods and Results: We utilized lung endothelial cells isolated from an ovine CHD model, created by the fetal placement of an aortopulmonary graft (Shunt). First, we confirmed that autophagy was activated in Shunt pulmonary artery endothelial cells (PAEC), with increased LC3-II/LC3-I ratio (1.45 fold increase, n=3, p&lt;0.05) and reduced p62 levels (64% reduction, n=3, p&lt;0.05). Shunt PAECs were found hyperproliferative (BrdU Assay A 450 : control vs. Shunt: 2.36 ± 0.05 vs . 2.58 ± 0.05, n=9, p&lt;0.01), which can be attenuated by pharmacologic autophagy inhibitor bafilomycin A1 (2.30 ± 0.05, n=9, p&lt;0.01 compared with Shunt) or 3-MA (2.20 ± 0.03, n=9, p&lt;0.001 compared with Shunt). Shunt PAECs exhibited significant endothelial Nitic Oxide Synthase (eNOS) uncoupling by BH4 reduction (31% reduction, n=3, p&lt;0.01). Bafilomycin A1 reversed eNOS uncoupling in Shunt PAECs by BH4 restoration (2.1 fold increase, n=3, p&lt;0.01), resulting in elevated cellular NOx level (1.8 increase fold, n=3, p&lt;0.01). Mechanistically, this was dependent on increased levels of GTP cyclohydrolase I (GCH1) protein in Shunt PAEC. Conclusions: Enhanced autophagy plays a key role in the loss of NO signaling and endothelial dysfunction associated with CHD. We speculate that autophagy might be an effective therapeutic target for pulmonary vascular diseases.